The purpose of these studies is to examine the mechanisms that have been postulated in mediating neurogenic pulmonary edema. Studies will be made in intact sheep in which the alterations in lung fluid and protein exchange and lung vascular permeability will be assessed. We will examine the effects of intracranial hypertension on lung vascular permeability, since studies indicate that intracranial hypertension increases permeability of lung microvessels to protein. This response will be characterized with respect to the threshold of the response, effects of raising intracranial pressure supratentorially or infratentorially, effects of sustained intracranial hypertension, and effects of varying the rate of intracranial hypertension. Other studies will examine the role of left atrial hypertension (sustained or transient) associated with intracranial hypertension, in mediating lung microvascular injury and leading to pulmonary edema. We will also test the hypothesis that severe transient bouts of left atrial hypertension, reported clinically after head injury, injure the endothelium and result in high permeability-pulmonary edema. The role of neurohumoral mechanisms (i.e., sympathetic and histamine) in mediating the increase in lung vascular permeability after intracranial hypertension will also be examined. Since cerebral ischemia has been postulated as a factor causing pulmonary edema, we will study in goats the effects of cerebral ischemia on lung fluid and protein exchange. Finally, we will examine the various cerebral and peripheral pathways which may mediate the increased permeability after intracranial hypertension. Hence, it will be possible to understand better the neurogenic influences on lung vascular permeability and the mechanisms by which these mediate pulmonary edema. Since we will examine the roles of the primary factors postulated in mediating neurogenic pulmonary edema, these studies will be of value in defining the pathogenesis of neurogenic pulmonary edema.